Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart

The expression and function of embryonic myosin heavy chain (eMYH) has not been investigated within the early developing heart. This is despite the knowledge that other structural proteins, such as alpha and beta myosin heavy chains and cardiac alpha actin, play crucial roles in atrial septal develo...

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Main Authors: Rutland, Catrin S., Polo-Parada, Luis, Ehler, Elisabeth, Alibhai, Aziza, Thorpe, Aaran, Suren, Suganthi, Emes, Richard D., Patel, Bhakti, Loughna, Siobhan
Format: Article
Published: Company of Biologists 2011
Online Access:https://eprints.nottingham.ac.uk/2451/
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author Rutland, Catrin S.
Polo-Parada, Luis
Ehler, Elisabeth
Alibhai, Aziza
Thorpe, Aaran
Suren, Suganthi
Emes, Richard D.
Patel, Bhakti
Loughna, Siobhan
author_facet Rutland, Catrin S.
Polo-Parada, Luis
Ehler, Elisabeth
Alibhai, Aziza
Thorpe, Aaran
Suren, Suganthi
Emes, Richard D.
Patel, Bhakti
Loughna, Siobhan
author_sort Rutland, Catrin S.
building Nottingham Research Data Repository
collection Online Access
description The expression and function of embryonic myosin heavy chain (eMYH) has not been investigated within the early developing heart. This is despite the knowledge that other structural proteins, such as alpha and beta myosin heavy chains and cardiac alpha actin, play crucial roles in atrial septal development and cardiac function. Most cases of atrial septal defects and cardiomyopathy are not associated with a known causative gene, suggesting that further analysis into candidate genes is required. Expression studies localised eMYH in the developing chick heart. eMYH knockdown was achieved using morpholinos in a temporal manner and functional studies were carried out using electrical and calcium signalling methodologies. Knockdown in the early embryo led to abnormal atrial septal development and heart enlargement. Intriguingly, action potentials of the eMYH knockdown hearts were abnormal in comparison with the alpha and beta myosin heavy chain knockdowns and controls. Although myofibrillogenesis appeared normal, in knockdown hearts the tissue integrity was affected owing to apparent focal points of myocyte loss and an increase in cell death. An expression profile of human skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the functional homologue of the chick eMYH gene. These data provide compelling evidence that eMYH plays a crucial role in important processes in the early developing heart and, hence, is a candidate causative gene for atrial septal defects and cardiomyopathy.
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spelling nottingham-24512020-05-04T16:31:15Z https://eprints.nottingham.ac.uk/2451/ Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart Rutland, Catrin S. Polo-Parada, Luis Ehler, Elisabeth Alibhai, Aziza Thorpe, Aaran Suren, Suganthi Emes, Richard D. Patel, Bhakti Loughna, Siobhan The expression and function of embryonic myosin heavy chain (eMYH) has not been investigated within the early developing heart. This is despite the knowledge that other structural proteins, such as alpha and beta myosin heavy chains and cardiac alpha actin, play crucial roles in atrial septal development and cardiac function. Most cases of atrial septal defects and cardiomyopathy are not associated with a known causative gene, suggesting that further analysis into candidate genes is required. Expression studies localised eMYH in the developing chick heart. eMYH knockdown was achieved using morpholinos in a temporal manner and functional studies were carried out using electrical and calcium signalling methodologies. Knockdown in the early embryo led to abnormal atrial septal development and heart enlargement. Intriguingly, action potentials of the eMYH knockdown hearts were abnormal in comparison with the alpha and beta myosin heavy chain knockdowns and controls. Although myofibrillogenesis appeared normal, in knockdown hearts the tissue integrity was affected owing to apparent focal points of myocyte loss and an increase in cell death. An expression profile of human skeletal myosin heavy chain genes suggests that human myosin heavy chain 3 is the functional homologue of the chick eMYH gene. These data provide compelling evidence that eMYH plays a crucial role in important processes in the early developing heart and, hence, is a candidate causative gene for atrial septal defects and cardiomyopathy. Company of Biologists 2011-09-15 Article PeerReviewed Rutland, Catrin S., Polo-Parada, Luis, Ehler, Elisabeth, Alibhai, Aziza, Thorpe, Aaran, Suren, Suganthi, Emes, Richard D., Patel, Bhakti and Loughna, Siobhan (2011) Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart. Development, 138 (18). pp. 3955-3966. ISSN 1477-9129 http://dev.biologists.org/content/138/18/3955.full doi:10.1242/dev.059063 doi:10.1242/dev.059063
spellingShingle Rutland, Catrin S.
Polo-Parada, Luis
Ehler, Elisabeth
Alibhai, Aziza
Thorpe, Aaran
Suren, Suganthi
Emes, Richard D.
Patel, Bhakti
Loughna, Siobhan
Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart
title Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart
title_full Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart
title_fullStr Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart
title_full_unstemmed Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart
title_short Knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart
title_sort knockdown of embryonic myosin heavy chain reveals an essential role in the morphology and function of the developing heart
url https://eprints.nottingham.ac.uk/2451/
https://eprints.nottingham.ac.uk/2451/
https://eprints.nottingham.ac.uk/2451/